title: Melanoma vaccine candidates from chimeric hepatitis B core virus-like particles carrying a tumor-associated MAGE-3 epitope.
abstract: Vaccination of melanoma patients with tumor-specific antigens recognized by cytotoxic T lymphocytes (CTLs) may produce significant tumor regressions. Here, we suggest a novel type of tumor vaccines, with well-studied CTL epitopes presented on highly immunogenic virus-like particle (VLP) carriers. Cancer-germline gene MAGE-3 encodes for an antigenic nonapeptide (MAGE-3(168-176) peptide) that is recognized by CTLs on human leukocyte antigen (HLA)-A1 and HLA-B35 molecules. A set of recombinant genes encoding hepatitis B virus core protein carrying MAGE-3 epitope was constructed and expressed in Escherichia coli cells. Variants that led to formation of chimeric VLPs in vivo were purified and analyzed for their DNA binding properties in vitro. VLPs exhibiting the most pronounced nucleic acid binding affinity were selected and loaded either with single-stranded DNA oligodeoxynucleotides rich in nonmethylated CG motifs, or with longer double-stranded DNA fragments. Packaged DNA was protected, at least partially, against the action of bacterial DNase. Such highly purified chimeric VLPs with entrapped immunomodulatory sequences could possibly be used as antitumor vaccines.
authors.affiliation: Latvian Biomedical Research and Study Center, Riga, Latvia. andris@biomed.lu.lv
authors.forename: Andris
authors.initials: A
authors.lastname: Kazaks
authors.forename: Reinis
authors.initials: R
authors.lastname: Balmaks
authors.forename: Tatyana
authors.initials: T
authors.lastname: Voronkova
authors.forename: Velta
authors.initials: V
authors.lastname: Ose
authors.forename: Paul
authors.initials: P
authors.lastname: Pumpens
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D003001:Cloning, Molecular; D018899:CpG Islands; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000628:therapy*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006512:Hepatitis B Core Antigens; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic